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2.
Nat Commun ; 12(1): 3291, 2021 06 02.
Article En | MEDLINE | ID: mdl-34078905

The formation of hyperphosphorylated intracellular Tau tangles in the brain is a hallmark of Alzheimer's disease (AD). Tau hyperphosphorylation destabilizes microtubules, promoting neurodegeneration in AD patients. To identify suppressors of tau-mediated AD, we perform a screen using a microRNA (miR) library in Drosophila and identify the miR-9 family as suppressors of human tau overexpression phenotypes. CG11070, a miR-9a target gene, and its mammalian orthologue UBE4B, an E3/E4 ubiquitin ligase, alleviate eye neurodegeneration, synaptic bouton defects, and crawling phenotypes in Drosophila human tau overexpression models. Total and phosphorylated Tau levels also decrease upon CG11070 or UBE4B overexpression. In mammalian neuroblastoma cells, overexpression of UBE4B and STUB1, which encodes the E3 ligase CHIP, increases the ubiquitination and degradation of Tau. In the Tau-BiFC mouse model, UBE4B and STUB1 overexpression also increase oligomeric Tau degradation. Inhibitor assays of the autophagy and proteasome systems reveal that the autophagy-lysosome system is the major pathway for Tau degradation in this context. These results demonstrate that UBE4B, a miR-9 target gene, promotes autophagy-mediated Tau degradation together with STUB1, and is thus an innovative therapeutic approach for AD.


Alzheimer Disease/genetics , Drosophila Proteins/genetics , MicroRNAs/genetics , Ubiquitin-Protein Ligases/genetics , tau Proteins/genetics , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Animals , Autophagy/genetics , Brain/metabolism , Brain/pathology , Cell Line, Tumor , Disease Models, Animal , Drosophila Proteins/metabolism , Drosophila melanogaster/genetics , Drosophila melanogaster/metabolism , Eye/metabolism , Eye/pathology , Humans , Lysosomes/metabolism , Mice , MicroRNAs/metabolism , Neurons/metabolism , Neurons/pathology , Phosphorylation , Proteasome Endopeptidase Complex/metabolism , Protein Processing, Post-Translational , Proteolysis , Ubiquitin-Protein Ligases/metabolism , Ubiquitination , tau Proteins/metabolism
3.
Mol Cells ; 43(3): 304-311, 2020 Mar 31.
Article En | MEDLINE | ID: mdl-31940717

Methionyl-tRNA synthetase (MRS) is essential for translation. MRS mutants reduce global translation, which usually increases lifespan in various genetic models. However, we found that MRS inhibited Drosophila reduced lifespan despite of the reduced protein synthesis. Microarray analysis with MRS inhibited Drosophila revealed significant changes in inflammatory and immune response genes. Especially, the expression of anti-microbial peptides (AMPs) genes was reduced. When we measured the expression levels of AMP genes during aging, those were getting increased in the control flies but reduced in MRS inhibition flies agedependently. Interestingly, in the germ-free condition, the maximum lifespan was increased in MRS inhibition flies compared with that of the conventional condition. These findings suggest that the lifespan of MRS inhibition flies is reduced due to the down-regulated AMPs expression in Drosophila.


Drosophila/genetics , Longevity/genetics , Methionine-tRNA Ligase/metabolism , Animals
4.
Urolithiasis ; 48(2): 151-158, 2020 Apr.
Article En | MEDLINE | ID: mdl-30868183

To investigate and compare surgical outcomes in totally tubeless percutaneous nephrolithotomy (ttPCNL) patients according to the type of sealant during nephrostomy tract closure, the records of 158 patients who underwent ttPCNL were retrospectively reviewed. Fibrin sealant [Tisseel®; n = 107, fibrin-only sealant (FS)] or gelatin matrix hemostatic sealant [FloSeal®; n = 51, gelatin matrix sealant (GS)] was applied during tract closure according to surgeon's preference. On the first postoperative day, computed tomography (CT) was scanned for all patients. Unsatisfactory radiological outcome (URO) was defined as any postoperative hematoma or urinoma (≥ 2 cm) on the CT. Unsatisfactory clinical outcome (UCO) was defined as any adverse event requiring additional intervention. Both UROs and UCOs were sub-classified as either hemorrhage or drainage related. 2:1 propensity score matching was applied according to clinical parameters. Median age was 58 (19-78) years and a mean stone size was 2.1 ± 1.1 cm. The treatment success rate (stone free or < 4 mm residual) among all patients was 91.1% (144/158). UROs and UCOs occurred in 35.4% (86/158) and 11.4% (18/158) of all cases, respectively. Neither of the frequency of URO nor hemorrhage-related UCO was different according to sealant type. However, drainage-related UCOs were more prevalent among the GS group, mainly due to the higher postoperative ureter stenting rate. The postoperative pain severity and the length of hospitalization were comparable between groups. In summary, using GS rather than FS during tract closure did not worsen hemorrhage-related outcomes. However, the clinical risk of ureter occlusion requiring additional temporary ureteral stenting was increased.


Hemostatics/adverse effects , Kidney Calculi/surgery , Nephrolithotomy, Percutaneous/adverse effects , Nephrostomy, Percutaneous/adverse effects , Postoperative Hemorrhage/epidemiology , Ureteral Obstruction/epidemiology , Adult , Aged , Female , Fibrin/administration & dosage , Fibrin/adverse effects , Gelatin/administration & dosage , Gelatin/adverse effects , Hemostatics/administration & dosage , Humans , Male , Middle Aged , Nephrolithotomy, Percutaneous/methods , Nephrostomy, Percutaneous/methods , Postoperative Hemorrhage/etiology , Postoperative Hemorrhage/prevention & control , Propensity Score , Retrospective Studies , Treatment Outcome , Ureteral Obstruction/etiology , Ureteral Obstruction/prevention & control , Young Adult
5.
J Urol ; 203(6): 1128-1134, 2020 06.
Article En | MEDLINE | ID: mdl-31845840

PURPOSE: The clinical implications of postoperative detection of circulating tumor cells in prostate cancer are largely unknown. We investigated the association between postoperative circulating tumor cell detection after radical prostatectomy and disease recurrence in prospectively enrolled patients with prostate cancer. MATERIALS AND METHODS: A total of 203 patients with an undetectable prostate specific antigen who had undergone radical prostatectomy for prostate cancer were prospectively enrolled. Circulating tumor cell sampling was performed at a median of 4.5 months after surgery. The primary end point was biochemical recurrence-free survival. Detection of circulating tumor cells in the blood of patients was performed using a novel approach with a replication-competent adenovirus controlled by prostate specific antigen/prostate specific membrane antigen transcription regulatory elements (Ad5/35E1aPSESE4). RESULTS: Circulating tumor cells were detected in 73 (36.0%) patients with undetectable prostate specific antigen concentrations after surgery. The 3-year biochemical recurrence-free survival rate from the time of surgery was significantly higher in circulating tumor cell-negative than in circulating tumor cell-positive cases (81.6% vs 48.9%, log rank p <0.001). Multivariable analysis showed that postoperative circulating tumor cell detection was independently associated with an increased risk of biochemical recurrence (HR 5.42, 95% CI 3.24-9.06, p <0.001). C-index was increased in combinations of multivariable model and postoperative circulating tumor cell detection compared with the multivariable model alone. CONCLUSIONS: Circulating tumor cells in the blood were frequently detected in patients with undetectable prostate specific antigen levels after radical prostatectomy for localized prostate cancer. Furthermore, circulating tumor cell detection was associated with an increased risk of biochemical recurrence, suggesting that circulating tumor cell detection precedes prostate specific antigen rise after surgery in cases of prostate cancer recurrence. Large-scale validation is needed in the future.


Biomarkers, Tumor/blood , Neoplasm Recurrence, Local/diagnosis , Neoplastic Cells, Circulating , Prostatectomy , Prostatic Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/pathology , Postoperative Care , Prospective Studies , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology
6.
Sci Rep ; 9(1): 6294, 2019 04 18.
Article En | MEDLINE | ID: mdl-31000756

This study aimed to compare the oncologic outcomes between retroperitoneal radical nephroureterectomy (rRNU) and transperitoneal radical nephroureterectomy (tRNU) for the treatment of patients with upper urinary tract urothelial carcinoma (UTUC). Medical records of 743 eligible patients who underwent rRNU or tRNU between 1995 and 2015 were reviewed retrospectively. Progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS) were compared according to the surgical approach using the Kaplan-Meier method. Predictors of PFS, CSS, and OS were analyzed with a multivariable Cox regression model. Overall, 620 (83.4%) and 123 (16.6%) patients were treated with rRNU and tRNU, respectively. Five-year CSS and OS rates were equivalent between rRNU and tRNU groups, but 5-year PFS was lower in the tRNU group than the rRNU group (P = 0.005). When patients were stratified by pathological T stage, PFS was significantly different between the two groups in favor of the rRNU group for both organ-confined disease (pTis/pTa/pT1/T2) (P = 0.022) and locally advanced disease (pT3/pT4) (P = 0.039). However, no significant differences in CSS or OS was observed when comparing the two surgical types in patients with organ-confined disease (P = 0.336 and P = 0.851) or patients with locally advanced disease (P = 0.499 and P = 0.278). tRNU was a significant predictor of PFS (hazard ratio = 1.54; P = 0.023), but not CSS or OS. Our findings indicate that the rRNU approach resulted in better PFS than the tRNU approach in patients with UTUC.


Carcinoma, Transitional Cell/surgery , Nephroureterectomy/adverse effects , Urologic Neoplasms/surgery , Urothelium/surgery , Aged , Carcinoma, Transitional Cell/physiopathology , Female , Humans , Laparoscopy/methods , Male , Middle Aged , Prognosis , Proportional Hazards Models , Retrospective Studies , Survival Rate , Urinary Tract/pathology , Urinary Tract/surgery , Urologic Neoplasms/physiopathology , Urothelium/physiopathology
7.
Sci Rep ; 9(1): 770, 2019 01 25.
Article En | MEDLINE | ID: mdl-30683879

Extra-transitional zone density (ETzD), a novel parameter is proposed to stratify the deviation of prostate specific antigen (PSA) due to structural change according to stromal hyperplasia of prostate. ETzD was conducted on a concept to estimate the PSA density (PSAD) after hypothetical enucleation of the transitional zone of an enlarged prostate by a non-linear regression prediction model with intrinsic linearity, from the retrospective analysis of PSA change observed actual enucleation by laser. The performance to predict the presence and severity of malignancy was validated by two cohorts of 3,440 prostate biopsies and 2,783 radical prostatectomy specimens. The performance of ETzD was compared with conventional parameters. The receiver operative curve of area under curve (AUC) of ETzD to predict the presence of malignacy was 0.862 (95% CI; 0.843~0.881), better than PSA, PSAD or transitional zone PSAD (TzPSAD). The AUC of ETzD to predict an unfavorable cancer among prostate cancer patients was 0.736 (95% CI; 0.705~0.768), which performs better than PSA and comparable to PSAD or TzPSAD. In summary, the performance of ETzD as a universal parameter to quantify the oncological hazard of a prostate was validated and the superiority to conventional parameters was verified.


Biomarkers, Tumor/metabolism , Prostate-Specific Antigen/metabolism , Prostate/pathology , Prostatic Hyperplasia/diagnosis , Prostatic Neoplasms/diagnosis , Aged , Algorithms , Biopsy , Cohort Studies , Humans , Male , Middle Aged , Prostatectomy , Retrospective Studies
8.
Oncotarget ; 9(41): 26291-26298, 2018 May 29.
Article En | MEDLINE | ID: mdl-29899859

OBJECTIVES: To investigate whether the preoperative detection of prostate stem cell antigen (PSCA) mRNA in blood has predictive value for biochemical recurrence, overall survival, and cancer-specific survival after radical prostatectomy in patients with high-risk prostate cancer. RESULTS: Median age was 67 years (interquartile range: 63-71), and median follow-up was 41 months (interquartile range: 25-65). PSCA mRNA was detected in 151 patients (51.1%). Biochemical recurrence was developed in 101 patients (34.2%), and all-cause mortality and prostate cancer-specific mortality occurred in 17 (5.7%) and 8 (2.7%) patients, respectively. Kaplan-Meier analysis revealed significant differences in biochemical recurrence, overall survival, and cancer-specific survival according to PSCA mRNA positivity. Cox regression hazards model analysis showed that PSCA mRNA positivity was an independent predictor of biochemical recurrence, overall survival, and cancer-specific survival. CONCLUSIONS: PSCA mRNA in the peripheral blood was related to poor prognosis. Detection of PSCA mRNA by polymerase chain reaction in peripheral blood can be used to predict survival after radical prostatectomy in patients with high-risk prostate cancer. Future study with larger cohort and long-term follow-up is required to confirm this finding. MATERIALS AND METHODS: A total of 295 patients with high-risk prostate cancer scheduled to undergo radical prostatectomy were prospectively enrolled from 2008 to 2016. Nested reverse transcription polymerase chain reaction was used to detect cells with PSCA mRNA in peripheral blood. The predicting ability of PSCA mRNA positivity for biochemical recurrence, overall survival, and cancer-specific survival after radical prostatectomy was evaluated.

9.
Low Urin Tract Symptoms ; 10(3): 231-236, 2018 Sep.
Article En | MEDLINE | ID: mdl-28436120

OBJECTIVE: To investigate the efficacy of Holmium laser transurethral incision of the prostate (Ho-TUIP) with preoperative characteristics based on urodynamic parameters. METHODS: The medical records of 40 consecutive cases of Ho-TUIP in patients unresponsive to medical treatment were retrospectively reviewed. The efficacy of Ho-TUIP was analyzed according to preoperative factors, including urodynamic parameters. Treatment success was confirmed if overall efficacy demonstrated an improvement that was "good or greater" according to the criteria developed by Homma et al. Predictive factors of treatment success were analyzed using logistic regression analysis with demographics, symptom questionnaires, prostate size, and urodynamic parameters. Postoperative complications and Global Response Assessment (GRA) were investigated. RESULTS: Mean age was 60.9 years (range 37-84), mean follow-up period was 36.6 months (range 6.3-114.8), and mean prostate size was 23.5 mL (range 12.7-39.5). All patients underwent medical treatment before Ho-TUIP, and mean medication duration was 50.5 months (range 3.4-140.0). The treatment success rate was 60.0%. Treatment success rates were higher in the bladder outlet obstruction index (BOOI) ≥20 group (n = 26) than in the BOOI <20 group (n = 14) (p = 0.003). In logistic regression analysis, BOOI ≥20 was a predictor of treatment success (OR 7.60, 95% CI 1.60-35.90, P = 0.010). Among patients who maintained an active sex life, 77.8% (14/18) reported retrograde ejaculation. In terms of GRA, 81.5% (31/38, two patients expired) of patients improved at the final follow-up. CONCLUSIONS: Ho-TUIP is an effective procedure with tolerable complications for the treatment of symptomatic mild-to-moderate BPE in patients with BOOI ≥20 that are unresponsive to medical treatment.


Lasers, Solid-State/therapeutic use , Lower Urinary Tract Symptoms/surgery , Prostate/pathology , Prostatic Hyperplasia/complications , Prostatic Hyperplasia/surgery , Adult , Aged , Aged, 80 and over , Ejaculation , Hematuria/etiology , Humans , Lower Urinary Tract Symptoms/etiology , Male , Middle Aged , Organ Size , Patient Selection , Postoperative Complications/etiology , Preoperative Period , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/pathology , Retreatment , Retrospective Studies , Treatment Outcome , Urinary Bladder Neck Obstruction/etiology , Urinary Bladder Neck Obstruction/surgery , Urinary Retention/etiology
10.
BJU Int ; 121(4): 659-666, 2018 04.
Article En | MEDLINE | ID: mdl-29232035

OBJECTIVE: To investigate the efficacy of endoscopic ablation of Hunner lesions (HLs) in patients with interstitial cystitis (IC) and to find predictors of early recurrence of HLs. PATIENTS AND METHODS: A prospective study was performed of patients with Hunner type IC who underwent transurethral ablation. We repeated endoscopic ablation when symptoms and HLs recurred during the follow-up period. The primary endpoint was recurrence-free time. Secondary endpoints were a change in frequency, nocturia, and urgency episodes, and changes in visual analogue scale (VAS) pain scores and other symptom indices at follow-up visits. RESULTS: A total of 72 patients were analysed. The median (range) follow-up period was 29.5 (12.0-50.0) months. After primary ablation treatment, HLs recurred in 75.0% (54/72) of patients, and the median (sd) recurrence-free time was 12.0 (1.6) months. Amongst the 54 patients with recurrence, 50 underwent a second ablation treatment. HLs occurred in 44.0% (22/50) of individuals after the second operation, and the median (sd) recurrence-free time was 18.0 (5.1) months. Lower maximal cystometric capacity (odds ratio 1.01, 95% confidence interval 1.001-1.013) was the predictive factor for early recurrence. There were significant improvements in the VAS pain scores, O'Leary-Sant Interstitial Cystitis Symptom Index and Problem Index, Pelvic Pain and Urgency/Frequency Patient Symptom Scale after treatment (all, P < 0.05). CONCLUSIONS: Endoscopic ablation is an effective treatment option for HLs and significantly reduces pain and improves voiding symptoms. Repeat ablation upon recurrence could help symptom control and bladder preservation only if the bladder capacity is maintained.


Ablation Techniques/methods , Cystitis, Interstitial/surgery , Endoscopy/methods , Aged , Cystitis, Interstitial/epidemiology , Female , Humans , Male , Middle Aged , Pelvic Pain/surgery , Prospective Studies , Recurrence , Treatment Outcome
11.
Urology ; 113: 215-219, 2018 Mar.
Article En | MEDLINE | ID: mdl-29030076

OBJECTIVE: To investigate the rates and predictive factors associated with the development of de novo overactive bladder (OAB) and to assess the effects of de novo OAB on surgical outcomes after an artificial urinary sphincter (AUS). MATERIALS AND METHODS: We performed a retrospective review of 132 patients with postprostatectomy incontinence who underwent AUS surgery. Urodynamic studies were performed during preoperative visits in all patients, and patients with OAB or neurogenic bladder were excluded. We assessed the development of de novo OAB based on patient symptoms. Treatment success was defined as no need for pads, and social continence was defined as the need for ≤1pad per day at the end of the follow-up. A multivariate analysis was performed using a logistic regression model to assess predictors of de novo OAB. RESULTS: The rate of development of de novo OAB after surgery was 37.5%. The treatment success rate was significantly higher in the no-OAB group (72.4%) than in the de novo OAB group (55.4%) (P = .038). A low preoperative cystometric capacity of less than 300 mL (odds ratio 5.27, confidence interval 1.02-27.28; P = .048) and pelvic irradiation (odds ratio 3.18, confidence interval 1.01-10.03; P = .049) were predictive factors of de novo OAB after AUS surgery. CONCLUSION: De novo OAB occurs commonly after AUS surgery, and the presence of de novo OAB adversely impacts treatment success. Low preoperative cystometric capacity of less than 300 mL and pelvic irradiation predict the occurrence of de novo OAB after AUS implantation.


Prostatectomy/adverse effects , Prosthesis Implantation/adverse effects , Urinary Bladder, Overactive/etiology , Urinary Incontinence/surgery , Urinary Sphincter, Artificial , Aged , Cohort Studies , Follow-Up Studies , Humans , Incidence , Kaplan-Meier Estimate , Logistic Models , Male , Middle Aged , Multivariate Analysis , Predictive Value of Tests , Prostatectomy/methods , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Prosthesis Implantation/methods , Retrospective Studies , Risk Assessment , Severity of Illness Index , Urinary Bladder, Overactive/epidemiology , Urinary Bladder, Overactive/physiopathology , Urinary Incontinence/etiology , Urinary Incontinence/physiopathology , Urodynamics
12.
Oncotarget ; 8(59): 100056-100065, 2017 Nov 21.
Article En | MEDLINE | ID: mdl-29245960

OBJECTIVE: To evaluate the progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) treated with double- and triple-sequence targeted therapy (TT) using tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin inhibitors (mTORi). MATERIALS AND METHODS: Records of 292 patients with mRCC, treated with TT between January 2005 and July 2015, were analyzed retrospectively. Kaplan-Meier and log-rank analyses were used to calculate and compare the total PFS (tPFS) and OS when patients underwent double- or triple-TT using TKIs or mTORi. RESULTS: Eighty-one (27.7%) patients who underwent second-line TT were enrolled; 30 (10.3%) of whom underwent third-line TT. The tPFS and OS of double-TT using TKI-mTORi (5.4 and 30 months, respectively) were significantly better compared with TKI-TKI (0.3 and 2 months) or mTORi-TKI (2 and 6 months) (p <0.001). For triple-TT, the tPFS and OS of TKI-mTORi-TKI (22.8 and 25 months, respectively) were significantly superior compared with those for TKI-TKI-mTORi (4 and 9 months) (p <0.05).For patients with intermediate-risk according to the Heng or Memorial Sloan-Kettering Cancer Center risk models, TKI-mTORi was associated with a significantly longer tPFS and OS compared with TKI-TKI [expect for OS in the Heng group (p = 0.086)]. For the triple TT group, TKI-mTORi-TKI resulted in improved tPFS and OS compared with TKI-TKI-TKI or TKI-TKI-mTORi (p <0.05). CONCLUSION: In patients with mRCC, sequential administration of TKI-mTORi led to a significantly superior tPFS compared with any other TT sequence. By contrast, OS did not differ significantly according to TT sequence.

13.
Oncotarget ; 8(55): 93633-93643, 2017 Nov 07.
Article En | MEDLINE | ID: mdl-29212178

INTRODUCTION: The aim of this study was to compare progression-free survival (PFS) and overall survival (OS) between metachronous and synchronous metastatic renal cell carcinomas treated with VEGF-targeted therapy. METHODS: Between 2005 and 2014, 93 (78.8%) intermediate- and 25 (21.2%) poor-Heng-risk patients, including 32 (27.1%) patients with metachronous and 86 (72.9%) patients with synchronous renal cell carcinoma, were enrolled retrospectively. PFS and OS values were compared according to the number of risk factors and treatment-free interval using the Kaplan-Meier method and log-rank test. The prognostic risk factors were also evaluated using a Cox proportional hazard model, with a p-value < 0.05 indicating statistical significance. RESULTS: During a median 5.0-month treatment and 59.3-month follow-up, analysis of the PFS/OS of SM (5.2/9.6 months) and MM (9.6/20.1 months) yielded a significant difference in OS (p = 0.010). However, there was no significant difference when Heng risk groups and treatment-free interval were considered (p > 0.05). There was a significant difference in PFS (hazard ratio: 1.81) and OS (hazard ratio: 2.19) with increasing number of Heng risk factors among patients with synchronous renal cell carcinoma and a treatment-free interval <1 year. Metastatic type, anemia, and neutrophilia were significant predictive factors for OS in multivariable analysis (p < 0.05). CONCLUSION: The metastatic type of renal cell carcinoma (synchronous or metachronous) significantly affects survival; metachronous type is associated with more favorable outcomes than synchronous type. However, after stratification according to Heng risk factors and treatment-free interval, the differences in survival between metachronous and synchronous type were insignificant.

14.
Biomed Res Int ; 2017: 7206307, 2017.
Article En | MEDLINE | ID: mdl-29230413

Prostate cancer (PC) is the second most common cancer in men and is the fifth leading cause of cancer-related deaths worldwide. Additionally, there is concern for overdiagnosis and overtreatment of PC. Thus, selection of an appropriate candidate for active surveillance as well as more accurate and less invasive tools for monitoring advanced PC is required. Circulating tumor cells (CTCs) have emerged as a liquid biopsy tool; there have been several reports on its role, technologies, and applications to various cancers, including PC. Liquid biopsy using CTCs has been gaining attention as a minimal invasive tool for investigation of biomarkers and for prognosis and assessment of response to therapies in patients with PC. Because of the lower invasiveness of liquid biopsy using CTCs, it can be performed more frequently; accordingly, personalized disease status can be successively determined at serial time points. CTC analysis enables detection of genomic alterations, which is drug-targetable, and it is a potential tool for monitoring response to therapeutic agents in patients with PC. This review focuses on the characteristics, technologies for analysis, and advantages and disadvantages of CTCs as a liquid biopsy tool and their application in PC. Finally, we propose future directions of CTCs.


Neoplastic Cells, Circulating/pathology , Prostatic Neoplasms/pathology , Biomarkers, Tumor/blood , Biopsy/methods , Humans , Male , Precision Medicine/methods
15.
Oncotarget ; 8(38): 64250-64262, 2017 Sep 08.
Article En | MEDLINE | ID: mdl-28969067

OBJECTIVE: The study was aimed to evaluate the prevalence and prognosis of prostate cancer (PC) and end-stage renal disease (ESRD), determine the risk factors for overall survival (OS) and PC-specific survival (CSS), and evaluate differences in PC-related clinical therapeutic patterns between patients with and without PC-ESRD. METHODS: This observational population study, performed at the National Cancer Center and Cancer Research Institute in Korea, included patients with PC and ESRD from the nationwide Korean Health Insurance System and Korean Central Cancer Registry data. Five-year overall and cancer-specific survival. A joinpoint regression analysis was performed to predict incidence and mortality of PC. Survival was analyzed using Kaplan-Meir curves with log rank tests of patients with dialysis or transplantation. RESULTS: Of 3945 patients with PC-ESRD, 3.9% were on dialysis (N=152), 0.2% had kidney transplantation (N=10, D-TPL group); 3783 (95.9%) had neither dialysis nor transplantation (non-D-TPL ESRD group). There were 697 PC-specific deaths. The median respective OS, PC-specific survival, and 5-year survival rates in the non-ESRD, non-D-TPL ESRD, dialysis ESRD, and transplantation ESRD groups were significantly different (p<0.001). Presence of ESRD, age, body mass index, SEER stage, no treatment within 6 months after diagnosis, no surgery, chemotherapy, radiotherapy or hormonal therapy, non-adenocarcinoma pathology, and Charlson comorbidity index were independent risk factors for OS and CSS. CONCLUSIONS: With a 10.1% nationwide prevalence of PC-ESRD, the presence of ESRD was a significant survival factor along with other significant clinicopathological factors.

16.
Int Neurourol J ; 21(3): 171-177, 2017 Sep.
Article En | MEDLINE | ID: mdl-28954458

PURPOSE: This study aimed to investigate potential biomarkers for the diagnosis of overactive bladder (OAB). METHODS: A total of 219 subjects were enrolled and divided into 2 groups: OAB subjects (n=189) and controls without OAB symptoms (n=30). Three-day voiding diaries and questionnaires were collected, and urinary levels of nerve growth factor (NGF), prostaglandin E2, and adenosine triphosphate were measured and normalized to urine creatinine (Cr). Baseline characteristics and urinary levels of markers were analyzed. A receiver-operator characteristic (ROC) curve was used to analyze the diagnostic performance of urinary markers. Urinary levels of markers according to subgroup and pathogenesis of OAB were evaluated. Correlation analyses were used to analyze the relationship between urinary levels of markers and voiding diary parameters and questionnaires. RESULTS: There was no difference between the 2 groups with regards to age, sex ratio, or urine Cr (P>0.05). The urinary levels of NGF/Cr were higher in OAB subjects than in controls (P<0.001). Urinary NGF/Cr was a sensitive biomarker for discriminating OAB patients (area under the curve=0.741; 95% confidence interval, 0.62-0.79; P=0.001) in the ROC curve. The urinary levels of NGF/Cr were significantly higher in OAB subjects than in controls regardless of subgroup or pathogenesis. Correlation analysis demonstrated urinary urgency was significantly related to urinary NGF/Cr level (correlation coefficient, 0.156). Limitations include a relatively wide variation of urinary markers. CONCLUSIONS: Urinary NGF is a potential biomarker that could serve as a basis for adjunct diagnosis of OAB.

17.
Sci Rep ; 7(1): 7523, 2017 08 08.
Article En | MEDLINE | ID: mdl-28790398

Abnormal aggregation of ß-amyloid (Aß) peptides is a major hallmark of Alzheimer's disease (AD). In spite of numerous attempts to prevent the ß-amyloidosis, no effective drugs for treating AD have been developed to date. Among many candidate chemicals, methylene blue (MB) has proved its therapeutic potential for AD in a number of in vitro and in vivo studies; but the result of recent clinical trials performed with MB and its derivative was negative. Here, with the aid of multiple photochemical analyses, we first report that photoexcited MB molecules can block Aß42 aggregation in vitro. Furthermore, our in vivo study using Drosophila AD model demonstrates that photoexcited MB is highly effective in suppressing synaptic toxicity, resulting in a reduced damage to the neuromuscular junction (NMJ), an enhanced locomotion, and decreased vacuole in the brain. The hindrance effect is attributed to Aß42 oxidation by singlet oxygen (1O2) generated from photoexcited MB. Finally, we show that photoexcited MB possess a capability to disaggregate the pre-existing Aß42 aggregates and reduce Aß-induced cytotoxicity. Our work suggests that light illumination can provide an opportunity to boost the efficacies of MB toward photodynamic therapy of AD in future.


Alzheimer Disease/drug therapy , Amyloid beta-Peptides/antagonists & inhibitors , Amyloidosis/drug therapy , Methylene Blue/pharmacology , Neuroprotective Agents/pharmacology , Nootropic Agents/pharmacology , Peptide Fragments/antagonists & inhibitors , Photosensitizing Agents/pharmacology , Alzheimer Disease/metabolism , Alzheimer Disease/physiopathology , Amyloid beta-Peptides/chemistry , Amyloid beta-Peptides/metabolism , Amyloidosis/metabolism , Amyloidosis/pathology , Amyloidosis/physiopathology , Animals , Brain/drug effects , Brain/metabolism , Brain/pathology , Disease Models, Animal , Drosophila melanogaster , Humans , Light , Locomotion/drug effects , Locomotion/physiology , Methylene Blue/chemistry , Methylene Blue/radiation effects , Neuromuscular Junction/drug effects , Neuromuscular Junction/metabolism , Neuromuscular Junction/pathology , Neuroprotective Agents/chemistry , Nootropic Agents/chemistry , Oxidation-Reduction , Peptide Fragments/chemistry , Peptide Fragments/metabolism , Photochemotherapy/methods , Photosensitizing Agents/chemistry , Protein Aggregates/drug effects , Singlet Oxygen/chemistry , Singlet Oxygen/pharmacology
18.
Int Neurourol J ; 21(2): 116-120, 2017 Jun.
Article En | MEDLINE | ID: mdl-28673059

PURPOSE: Many surgeons worry about postoperative voiding problems in patients with stress urinary incontinence (SUI) and detrusor underactivity (DU). This study hypothesized that adjusting the tension after surgery would benefit patients with DU, and therefore researchers evaluated the outcomes and quality of life of women with SUI and DU who underwent the readjustable sling procedure (Remeex). METHODS: The medical records of 27 patients who were treated with the Remeex system for SUI and DU between 2007 and 2013 were retrospectively analyzed. The incontinence visual analogue scale (I-VAS), incontinence quality of life questionnaire (I-QOL) and the Sandvik incontinence severity index (ISI) were used to evaluate the efficacy of the Remeex system both prior to surgery and at the last visit after surgery. The treatment was considered successful if there was no urine leakage based on the Sandvik questionnaire. RESULTS: The mean follow-up period was 38.0 months (range, 1-75 months), and the treatment success rate was 81.5%. Despite no urine leakage, 7 patients wanted the Remeex system to be removed due to persistent postoperative urinary retention within a year of surgery. One patient underwent a long-term adjustment under local anesthesia 6 years after the initial surgery. The I-VAS, ISI and all domains of the I-QOL scores improved significantly postoperatively and the maximum flow rate decreased significantly after the procedure. However, the postvoid residual did not change significantly. CONCLUSIONS: The Remeex system provided a good cure rate and improved the quality of life of women with SUI and DU. Therefore, the Remeex system should be considered as a treatment option for female patients with concomitant SUI and DU.

19.
Int J Clin Pract ; 71(5)2017 May.
Article En | MEDLINE | ID: mdl-28508459

OBJECTIVES: The aim of this study was to evaluate the pattern of tailoring and efficacy of several types of pharmacotherapy in male LUTS. METHODS: Prospectively 404 male subjects were included who were over 40 years old, had at least 3 months symptom duration, and 12 or higher international prostate symptom score (IPSS). Subjects were treated with several types of pharmacotherapy for 6 months and were evaluated with IPSS/QoL at every follow-up. Subjects were subdivided into storage (44%), nocturia (18.5%), and voiding symptom (37.5%) groups according to the most bothersome symptom. RESULTS: At 6 months, 188 subjects (46.5%) completed the study. The mean age was 64.2±8.5 years, and symptom duration was 30.6±32.6 months. PSA was 2.98±7.96 ng/mL, and prostate size was 32.8±14.2 cc. IPSS continually decreased from baseline (18.7) to last follow-up (10.8). Combination therapy increased from 33.0% to 52.7% at last follow-up (P=.006). However, there was no difference of IPSS changes between combination and monotherapy groups (P>.05). Only antimuscarinic prescription significantly increased from 15.4% to 28.2% (P=.004). Mean number of visits to the clinic was 3.6±1.3 and the number of treatment changes was 0.31±0.47. The nocturia (0.47±0.51) group changed treatment more than voiding group (0.21±0.41, P=.003). However, the voiding group (-9.4) had significantly more improvement than e storage (-6.4) and nocturia (-7.8) groups (P=.011). CONCLUSIONS: Male LUTS continually improved over 6 months with customised treatment. Pharmacotherapy for male LUTS should be tailored by symptom type and alteration of symptoms during treatment.


Lower Urinary Tract Symptoms/drug therapy , Muscarinic Antagonists/therapeutic use , Practice Patterns, Physicians'/statistics & numerical data , Urological Agents/therapeutic use , Adult , Aged , Aged, 80 and over , Drug Therapy, Combination , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Republic of Korea , Treatment Outcome
20.
Int Neurourol J ; 21(1): 68-74, 2017 Mar 24.
Article En | MEDLINE | ID: mdl-28361513

PURPOSE: This study aimed to investigate the surgical outcomes and safety of robotic sacrocolpopexy (RSC) in patients with uterine/vaginal vault prolapse. METHODS: Between January 2009 and June 2015, 16 women with apical prolapse underwent RSC. Pelvic organ prolapse quantification (POP-Q) examination was performed, and treatment success was defined as the presence of grade 0 or I apical prolapse upon POP-Q examination at the final follow-up. Pelvic floor distress inventory-short form 20 (PFDI-SF 20) was administered at every follow-up. A treatment satisfaction questionnaire was administered by telephone to evaluate patient satisfaction with the operation. RESULTS: Median age was 65 years (interquartile range [IQR], 56-68 years), and follow-up duration was 25.3 months (IQR, 5.4-34.0 months). Thirteen women (81.3%) had ≥grade III apical prolapse. Operation time was 251 minutes (IQR, 236-288 minutes), and blood loss was 75 mL (IQR, 50-150 mL). Median hospital stay was 4 days (IQR, 3-5 days). At the final follow-up, treatment success was reported in all patients, who presented grade 0 (n=8, 57.1%) and grade I (n=6, 42.9%) apical prolapse. Dramatic improvements in PFDI-SF 20 scores were noted after RSC (from 39 to 4; P=0.001). Most patients (12 of 13) were satisfied with RSC. An intraoperative complication (sacral venous plexus injury) was reported in 1 patient, and there was no conversion to open surgery. Mesh erosion was not reported. CONCLUSIONS: RSC is an efficient and safe surgical option for apical prolapse repair. Most patients were satisfied with RSC. Thus, RSC might be one of the best treatment options for apical prolapse in women.

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